Epigenetic silencing of critical genes through aberrant methylation appears to play a key role in tumor[unreadable] development. To advance our basic understanding of the epigenetic regulation of gene expression in cancer[unreadable] cells, and clinically test the hypothesis that remethylation of genes has therapeutic potential, we will[unreadable] investigate chronic lymphocytic leukemia (CLL) as a model in the projects presented in this program project[unreadable] proposal. However, the ability to meaningfully conduct basic studies and translate important findings to the[unreadable] clinical setting is greatly facilitated by the availability of an extensive repository of tissue samples, with[unreadable] accompanying pathologic and clinical data, procured from relevant patients CLL. This Core, the[unreadable] Pathology/Tissue Procurement Core, through the collaboration of the OSU Leukemia Tissue Bank (LTB),[unreadable] will serve this function in supporting the basic and clinical projects of this Program Project. The OSU leukemia[unreadable] tissue bank has a well-established infrastructure directly under our leadership. The Core will participate in the[unreadable] procurement of procurement of CLL cells and the molecular characterization of CLL cases for the Projects. All[unreadable] the essentials of effective tissue bank management, including the activities of tissue collection, quality control[unreadable] of specimens, tissue storage, procurement of initial and follow-up samples and their pathology and clinical[unreadable] information, data entry and database management, and patient consent and confidentiality are very well[unreadable] developed in this Core. In addition, this Core has the established capacity to process procured specimens for[unreadable] the preparation of pure cell populations (e.g., CLL cells though CD19 positive selection), cell lysates, nucleic[unreadable] acids and proteins in a uniform manner for ready distribution to investigators. Furthermore, the procedures for[unreadable] prioritizing and distributing tissue to a large base of investigators, within and outside our institution, are[unreadable] effectively in place. Against this background, we believe that this Core will function well in the support of the[unreadable] 5 projects proposed in this application, as well as future projects and collaborations. While funding currently[unreadable] exists for the infrastructure of OSU LTB, it is emphasized that there is no overlap in funding requested for this[unreadable] Core, as all of the new work proposed in this Program Project is not currently funded by NCI or other peer[unreadable] reviewed grants. The Specific Aims of this Core are, therefore, to: 1) provide central collection, processing[unreadable] and a state-of-the-art repository for samples collected from CLL patients treated at OSU, including protocols[unreadable] relevant to this Program Project; 2) provide materials from processed CLL samples for the support of Projects[unreadable] 1-5 of this Program Project proposal in a standardized manner, and 3) perform molecular characterization,[unreadable] including cytogenetic fluorescent in-situ hybridization (FISH) studies, lgVH and p53 mutational status, on all[unreadable] CLL cases used in the Projects to permit subsequent correlation with clinical and laboratory results.[unreadable]